The overall goal of this research is to study relationships of genetics, structure, and function of hemoglobins. The work will focus on the following five objectives: studies of the genetic control of hemoglobin structure; structural characterization of new abnormal hemoglobins; determination of the amino acid sequence of the zeta chain of a human embryonic hemoglobin (Hb portland 1); determination of the structure of selected animal hemoblobins; and the correlation of structure to altered chemical properties and biological function of abnormal human hemoglobins in an attempt to better understand structure- function relationships at the molecular level. These objectives will be pursued by the chemical characterization of abnormal hemoglobins selected because they appear to be new and previously unreported mutants or because they are previously reported mutants but are found in informative family arrangements or are observed to have interesting but previously unreported properties. The majority of these are expected to be obtained from referral sources which already exist and will be studied and reported in collaboration with the referring people. The zeta chain will be isolated from Hb Portland 1 obtained from stillbirth infants with hydrop fetalis or from cord blood of infants in which this hemoglobin can be detected. Animal hemoglobins will be selected because of special genetic or evolutionary reasons or because of unusual chemical properties in comparison to human hemoglobins. Methods to be used in this research include chromatographic isolation of single hemoglobin components, polypeptide chain separation, automatic chromatographic separation and purification of peptide fragments, automatic amino acid analysis, and manual and automatic Edman sequence analysis.